PROJECT SUMMARY/ABSTRACT With the introduction of reduced intensity conditioning (RIC) regimens, allogeneic hematopoietic stem cell transplantation (alloHCT) is now a viable treatment option for many older myelodysplastic syndrome (MDS) patients. While alloHCT is the only curative treatment option for MDS, the costs and risks associated with the procedure have to be weighed against potential life-years gained and compared to alternatives such as treatment with hypomethylating agents ([HMA] azacitadine and decitabine). A prospective, comparative biologic assignment trial (BMT CTN 1102) is now studying RIC alloHCT from related and unrelated donors versus HMA or best supportive care among patients with Intermediate-2/High risk MDS aged 50-75 years. The clinical study will test the hypothesis that three-year overall survival is higher in the alloHCT am than in the HMA and best supportive care arm. The findings of BMT CTN 1102 have the potential to expand access to and Medicare coverage of alloHCT to older MDS patients. Given that alloHCT is one of the costliest procedures in medicine today, there are profound implications for health care payers, patients, and society. Uncertainty about the risks of alloHCT, specifically graft versus host disease and other complications, quality of life, and its high cost associated with the procedure and the treatment of potential complications provide a compelling case for conducting a cost- effectiveness analysis (CEA) comparing alloHCT to HMA and best supportive care. Conducting an ancillary CEA alongside BMT CTN 1102 provides the opportunity to precisely measure a range of quality of life and expenditure endpoints to complement the clinical endpoints evaluated in the parent trial. By prospectively enrolling patients into the CEA, patients and their caregivers can be surveyed while they are experiencing the economic consequences of treatment, reducing recall bias and enhancing validity. This is a time-sensitive opportunity to explore the cost-effectiveness of these two alternative options. In order to efficiently collect prospective data from participants in BMT CTN 1102, the ancillary CEA will work with the parent study to recruit patients and follow a similar data collection schedule. In summary, the proposed study will be the first to provide a comprehensive evaluation of the potential cost- effectiveness of alloHCT compared to HMA and best supportive care for the treatment of older MDS patients. To evaluate the economic Impacts of these two strategies from multiple perspectives, insurance claims records will be combined with direct patient surveys, to capture out-of-pocket and non-medical expenditures. The findings of this ancillary CEA may be used by patients, clinicians, and health insurers working with limited resources to assist in decisions about alternative MDS treatment strategies.